Caries, periodontal disease, disfigurement, mucosal pathology and occasional development of B cell lymphomas result from salivary gland disorders (SGD) such as Sjorgren's Syndrome and a related HIV SGD. These diseases are autoimmune disorders with an unknown cause and no known cure. Recently, the Webster-Cyriaque lab has shown that polyomavirus BK viral gene products are consistently found in SGD. We believe that BK virus (BKV) infection or reactivation is a factor in disrupting cellular processes leading to the development of SGD. The goal of this proposal is to aid the Webster-Cyriaque lab in determining the cause of SGD by creating a BKV-salivary gland computational model. In this project I will build an agent-based model to test theories about virus-host interactions that induce an antigen response. In an ABM, proteins, RNAs, DNA, etc. are represented as independent entities termed agents. Agents are small, independent information carrying automata that interact randomly with other agents. Agents move by mimicking the erratic random movement of biological elements as if bombarded by molecules in a virtual cellular environment. When an agent encounters other agents, rules for interaction between agents are exercised easily modeling stochastic events and interactions in biology, such as in the formation of a protein dimer. Models are built from the bottom-up by specifying individual components, such that complex behaviors emerge at the cellular level. Models can be built at multiple scales, by representing a complete ABM as an agent in a higher-order model-a model of models. I propose a multi-scale, bottom-up model of BKV-salivary gland cell interaction as follows: a) Create a BKV model formed of agents representing the DNA genome and capsid proteins, VP1, VP2 and VPS. This is necessary to understand the interaction of the capsid proteins during viral entry and self assembly of virions. b) Create salivary gland cell model with structures representing the Golgi apparatus, endoplasmic reticulum, cytoskeleton and nucleus. Agents will represent elements involved in cell cycle signalling pathways which interact with Large t antigen and small t antigen, c) BKV model interacting with salivary gland cell model. Models from a) and b) will be combined to study virus-host interaction. Agents will interact to model caveolae-mediated endocytosis, transport to the nucleus, virus replication, virus assembly and virus egress to infect other cells. In sum, I hope to advance research into the cause of SGD by developing a computational model that can be used to examine theories about interacting virus-host proteins and molecules.